摘要
背景:ATP结合盒(ABC)转运蛋白介导的多药耐药(MDR)仍然是有效癌症治疗的主要障碍。基于纳米颗粒(NPs)的递送系统有望克服MDR,但其中只有少数已被接受用于临床治疗,这应该是由于它们的运输不足和潜在的毒性。在这方面,人们越来越关注NPs和ABC转运蛋白之间的相互作用,这些转运蛋白在MDR癌症的治疗和NPs的毒性中起着关键作用。但是,没有关于这种相互作用的系统评价,特别是关于它们相应的机制。 方法:我们使用重点评论问题对PubMed数据库进行了广泛的搜索,以获得同行评审的文献。检索到的论文大多在5年内发表(104篇中的84篇),影响因子均高于2.首先,本综述重点介绍了参与MDR及其抑制剂的ABC转运蛋白的现有知识。然后,我们回顾了最近关于有机NPs赋形剂对ABC转运蛋白的抑制作用以及无机NPs与ABC转运蛋白的直接相互作用的文献。根据NP的结构描述和分类获得的论文的主要元素。 结果:有机和无机NP均能抑制ABC转运蛋白的功能,但基于不同的机制。有机纳米颗粒的作用是由几种赋形剂引起的,如表面活性剂,聚合物,脂质和环糊精。同时,无机NP通常作为ABC转运蛋白的底物并且竞争性地抑制药物的流出。这些现象很有意思,值得研究。 结论:该评价的发现证实了NP和ABC转运蛋白之间的潜在相互作用。这些现象很有意思,值得研究,相关机制的知识不仅对于克服癌症MDR的临床疗法很重要,而且还有助于治疗其他疾病,如结核病,艾滋病和中枢神经系统疾病,其耐药性是也与ABC转运蛋白介导的外排有关。
关键词: 癌症,多药耐药,ABC转运蛋白,有机纳米粒,无机纳米粒,艾滋病。
Current Medicinal Chemistry
Title:Current Understanding of Interactions between Nanoparticles and ABC Transporters in Cancer Cells
Volume: 25 Issue: 42
关键词: 癌症,多药耐药,ABC转运蛋白,有机纳米粒,无机纳米粒,艾滋病。
摘要: Background: ATP-binding cassette (ABC) transporters-mediated multidrug resistance (MDR) remains the major obstacle for effective cancer therapy. Nanoparticles (NPs)-based delivery systems are promising to overcome MDR, but only a few of them have been accepted for clinical treatment, which should be due to their insufficient transportation and potential toxicity. In this respect, more and more attentions are being attracted on the interactions between NPs and ABC transporters, which hold a key role in the treatment of MDR cancer and the toxicity of NPs. However, there are no systematic reviews about such interactions, especially about their corresponding mechanism.
Methods: We undertook extensive search of PubMed databases for peer-reviewed literatures using focused review questions. The retrieved papers were mostly published within the 5 years (84 of 104) and all with an impact factor above 2. First, this review focused on the current knowledge of ABC transporters involved in MDR and their inhibitors. Then, we reviewed the most recent literature about the inhibitory effects of organic NPs’ excipients on ABC transporters and the direct interactions of inorganic NPs with ABC transporters. The major elements of obtained papers were described and classified depending on the structure of NPs.
Results: Both organic and inorganic NPs can inhibit the function of ABC transporters, but based on different mechanisms. The effects of organic NPs are caused by several excipients like surfactants, polymers, lipids and cyclodextrin. Meanwhile, inorganic NPs usually act as the substrates of ABC transporters and competitively inhibit the efflux of drugs. These phenomena are interesting and worth investigating.
Conclusion: The finding of this review confirmed the potential interactions between NPs and ABC transporters. These phenomena are interesting and worth investigating, and a knowledge of related mechanism would not only be important for the clinical therapies toward overcoming cancer MDR, but also help the treatment of other diseases like tuberculosis, AIDS, and central nervous system disorders, whose drugresistance was also related to ABC transporter-mediated efflux.
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Current Understanding of Interactions between Nanoparticles and ABC Transporters in Cancer Cells, Current Medicinal Chemistry 2018; 25 (42) . https://dx.doi.org/10.2174/0929867325666180314122200
DOI https://dx.doi.org/10.2174/0929867325666180314122200 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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